Keratinocyte-Immune Cell Crosstalk in a STAT1-Mediated Pathway: Novel Insights Into Rosacea Pathogenesis
| Autor: | Zhili Deng, Fangfen Liu, Mengting Chen, Chuchu Huang, Wenqin Xiao, Sini Gao, Dan Jian, Yuyan Ouyang, San Xu, Jinmao Li, Qian Shi, Hongfu Xie, Guohong Zhang, Ji Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Keratinocytes 0301 basic medicine Immunology keratinocyte Biology Skin Diseases Pathogenesis 03 medical and health sciences 0302 clinical medicine Immune system STAT1 skin inflammation medicine Humans Immunology and Allergy RNA-Seq Original Research Skin Epithelial cell differentiation integumentary system Gene Expression Profiling epithelial-immune cell crosstalk Middle Aged RC581-607 medicine.disease Immunity Innate rosacea Crosstalk (biology) AP-1 transcription factor STAT1 Transcription Factor 030104 developmental biology medicine.anatomical_structure IRF1 pathogenesis 2 Rosacea 030220 oncology & carcinogenesis Cancer research Female Immunologic diseases. Allergy Keratinocyte Transcription Factors |
| Zdroj: | Frontiers in Immunology, Vol 12 (2021) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2021.674871/full |
| Popis: | Rosacea is a common chronic inflammatory condition that mainly affects the central face. However, the molecular background of the normal central face and the transcriptional profiling and immune cell composition of rosacea lesions remain largely unknown. Here, we performed whole-skin and epidermal RNA-seq of central facial skin from healthy individuals, lesions and matched normal skin from rosacea patients. From whole-skin RNA-seq, the site-specific gene signatures for central facial skin were mainly enriched in epithelial cell differentiation, with upregulation of the activator protein-1 (AP1) transcription factor (TF). We identified the common upregulated inflammatory signatures and diminished keratinization signature for rosacea lesions. Gene ontology, pathway, TF enrichment and immunohistochemistry results suggested that STAT1 was the potential core of the critical TF networks connecting the epithelial–immune crosstalk in rosacea lesions. Epidermal RNA-seq and immunohistochemistry analysis further validated the epithelial-derived STAT1 signature in rosacea lesions. The epidermal STAT1/IRF1 signature was observed across ETR, PPR, and PhR subtypes. Immune cell composition revealed that macrophages were common in all 3 subtypes. Finally, we described subtype-specific gene signatures and immune cell composition correlated with phenotypes. These findings reveal the specific epithelial differentiation in normal central facial skin, and epithelial–immune crosstalk in lesions providing insight into an initial keratinocyte pattern in the pathogenesis of rosacea. |
| Databáze: | OpenAIRE |
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